Essential role of the amino-terminal region of Drosha for the Microprocessor function
eScholarship, University of California, 2022
Online
academicJournal
Summary: The ribonuclease (RNase) III enzyme Drosha enables processing of microRNA (miRNA) primary transcripts (pri-miRNAs) and control of ribosomal protein (RP) biogenesis by the Microprocessor. The extensively studied carboxyl-terminal half of Drosha is sufficient to crop pri-miRNAs in vitro, but the function of the evolutionarily conserved Drosha amino-terminal region (NTR) is unknown, despite it harboring mutations linked to a hereditary vascular disorder. Here, we provide evidence that, when replacing the endogenous Drosha, a mutant missing the NTR (ΔN-Drosha) fails to associate with endogenous pri-miRNAs and to support the expression of all miRNAs, except the miR-183 cluster. Surprisingly, Argonaute2 (Ago2) associates with and cleaves pri-miR-183 in ΔN-Drosha cells and in Drosha-depleted cells. ΔN-Drosha is also unable to inhibit RP biogenesis upon serum starvation. Thus, Drosha NTR is essential for pri-miRNA processing and RP biogenesis in vivo, and Ago2 can process the miR-183 cluster in the absence of Drosha.
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Essential role of the amino-terminal region of Drosha for the Microprocessor function
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| Autor/in / Beteiligte Person: | Prabhakar, Amit ; Hu, Song ; Tang, Jin ; Ghatpande, Prajakta ; Lagna, Giorgio ; Jiang, Xuan ; Hata, Akiko |
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| Veröffentlichung: | eScholarship, University of California, 2022 |
| Medientyp: | academicJournal |
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